tbuckley/cabot-search huggingface dataset:
Abstract 13175: The Effect of Impella Placement on Morbidity and Mortality in Cardiogenic Shockcomparing Outcomes of Two Percutaneous Mechanical Circulatory Support Modalities as Bridges to Advanced Heart Failure Therapy
Authors: John DeStefano, Payton Kendsersky, Molly Silkowski, Emily Ramsayer, Megan Minchak, Matt Evans, William C Mostertz, Arasi Maran, Chris Nielsen, VALERIAN Fernandes
Journal: Circulation (2022)

Objectives: The use of percutaneous mechanical circulatory support (PMCS) devices offers a means to maintain hemodynamic stability in pre-transplant patients. The Impella Heart Pump and the intra-aortic balloon pump (IABP) are two devices commonly employed for this purpose. We sought to compare the relative safety and efficacy of Impella vs IABP using a retrospective cohort of patients at our institution from 2014-2021. Methods: 239 patients received Impella support, and 220 patients received IABP. Of these patients, 26 receiving Impella and 49 receiving IABP were identified as pre-transplant/VAD. The incidences of 30-day mortality, major bleeding, hemolysis, limb ischemia, stroke, repositioning, and infection were recorded. The number of patients receiving transplants, VADs, Mechanical Circulatory Support escalation, and ECMO were also recorded. The relative risks of complications were calculated, and an alpha of 0.05 was assigned to identify significance. Results: The average age of the IABP group was 54.8 +/- 12.1 years with 39 males to 10 females. The average age of the Impella group was 44.8 +/- 15 years with 15 males to 11 females. There was no significant difference in pre-placement EF between these two groups (IABP EF = 19.28+/-8.62, Impella EF = 21.15+/-9.69; p = 0.4016). A significantly higher relative risk of mortality (RR = 3.23; 95% CI = 1.45-7.20, p = 0.0041), major bleeding (RR = 8.48; 95% CI = 3.2 - 22.45, p &lt; 0.00001), and hemolysis (RR = 35.2; 95% CI = 2.12-582, p = 0.0128) was noted in patients receiving Impella support. No significant difference in the incidence of limb ischemia, stroke, repositioning, or infection was observed between these two groups. A significantly higher number of patients receiving Impella support also required ECMO (p = 0.0003) Conclusions: These data suggest that a higher risk of mortality or major complications may exist for patients receiving Impella support pre-transplant/VAD. Further analysis is needed to correct for baseline differences between these two cohorts.
Abstract 14802: Influence of Coronary Artery Anomalies on Left Ventricle Function After Arteries Switch Operation: A Two-Dimensional Speckle Tracking Echocardiography Study
Authors: Shuyuan Wang, Yanting Zhang, Wei Sun, Li Zhang, Qing Lv, Mingxing Xie
Journal: Circulation (2022)

Background: This study aimed to assess the influence of the complexity of coronary arteries (CA) anomalies and high-risk CA on Left ventricular (LV) function after arterial switch operation (ASO) using two-dimensional speckle-tracking echocardiography. Methods: Sixty patients with transposition of the great arteries after ASO who underwent echocardiography performed between January 2007 and June 2021 and thirty controls were studied. Patients after ASO were categorized into three subgroups: usual CA group ( n = 30), low-risk CA group ( n = 22), and high-risk CA group ( n = 8). LV longitudinal strain (LS) at the apical four-chamber view was analyzed. Results: Compared with controls, age at echocardiography examination (5.5 ± 3.1 years vs. 7.5 ± 3.9 years, P = 0.008) and body surface area (median 0.8 m 2 vs. 1.0 m 2 , P = 0.033) were smaller in ASO group. Patients after ASO had significantly lower septal e’ (10.9 ± 1.3 cm/s vs. 13.7 ± 2.2 cm/s, P &lt; 0.001), a’ (5.3 ± 0.8 cm/s vs. 7.2 ± 1.6 cm/s, P &lt; 0.001), and s’ (5.9 ± 0.9 cm/s vs. 8.4 ± 1.5 cm/s, P &lt; 0.001), and greater E/e’ (10.3 ± 2.4 vs. 8.0±1.7, P &lt; 0.001) than controls. Patients after ASO had normal and comparable LV ejection fraction (63.3 ± 4.7% vs. 63.0 ± 5.1%, P = 0.771), while LV LS were significantly lower (-20.9 ± 2.4% vs. -24.2 ± 2.0%, P &lt; 0.001) to controls. LV ejection fraction was similar among usual, low-risk, and high-risk CA groups (64.2 ± 4.6% vs. 62.3 ± 4.8% vs. 62.9 ± 4.8%, P = 0.557), while LV LS was significantly lower in high-risk CA group (-18.3 ± 2.6% vs. -21.5 ± 2.1% vs. -21.1 ± 2.2%, P &lt; 0.001). LV LS was negatively correlated with the level of complexity of CA anatomy ( r = -0.288, P = 0.026) and positively correlated with septal E/e’ ( r = 0.268, P = 0.038). Conclusion: LV systolic and diastolic function were generally normal, however, significantly lower in patients at 5 years after ASO than in healthy peers. Patients with high-risk CA are associated with greater impairment of ventricular systolic myocardial deformation.
Abstract 12968: Survival of a Left Ventricular Free Wall Rupture in a 52-Year-Old Female
Authors: Christopher Stancic, Lydia Meece, Danielle Gilbert, russell hamilton
Journal: Circulation (2022)

Introduction: Ventricular free wall rupture is an often fatal STEMI complication that has become increasingly rare thanks to early treatment of STEMI with primary percutaneous coronary intervention. Mortality is extremely high, with survival being dependent on early diagnosis and intervention as demonstrated in our case. Case: A 52 year old female with multi-vessel CAD and current tobacco use presented for acute, severe chest pain radiating to the jaw, throat, and upper back. She had been discharged the day prior after being medically managed for an inferior STEMI that had poor distal targets for CABG. Chest pain had been improving at time of discharge, but acutely worsened again the day of presentation and was accompanied by dyspnea. BP was persistently hypotensive despite aggressive fluid resuscitation. Physical exam was notable for diffuse tenderness of chest wall. Patient was alert and oriented. Troponin was down-trending from initial inferior infarct but still elevated. EKG still showed inferior infarct with no new changes. CTA chest, abdomen, and pelvis demonstrated hemopericardium and a linear focus of contrast enhancement involving the inferior left ventricular wall was seen on post-contrast images as shown in Figure 1. Patient was emergently taken to OR where intraoperative TEE with color doppler demonstrated color flow across the mid inferolateral wall consistent with myocardial perforation as seen in Figure 2. The hemopericardium was evacuated, a single-vessel coronary artery bypass-SVG to RPL was performed, and the myocardial rupture was closed with a pericardial patch. Patient survived and remained in the ICU for 10 days before being discharged.
Abstract 15376: Nrf2 Agonist Omaveloxolone Improves Cardiac Function in Mice With Friedreich's Ataxia
Authors: Francisco Figueroa, Lili Salinas, Claire Montgomery, Phung Thai, Nipavan Chiamvimonvat, Gino Cortopassi, Elena N Dedkova
Journal: Circulation (2022)

Introduction: Friedreich’s ataxia (FA) is an inherited, life-shortening, degenerative neuromuscular disorder affecting ~1 in every 50,000 people in the USA and Europe. Initial symptoms, typically seen in children and teenagers, include loss of balance and coordination, muscle weakness placing these patients in wheelchairs. Early death is common and most of FA patients die in their 30s or earlier from cardiac failure, caused by deficient frataxin (FXN) expression in the heart. Omaveloxolone (OMAV), a known Nrf-2 activator, has been recently proposed as the first treatment of the neurological symptoms of FA; however less is known about OMAV effects on cardiac function in FA. Aim: To test the hypothesis that OMAV improves cardiac function in a mouse model of FA via Nfr2 signaling pathway activation. Methods and Results: Cardiospecific FXN knockout (FXN Mck-Cre KO) mice were used as a model of severe cardiomyopathy which is characteristic for the late stage of FA. Animals of either sex were randomly split in vehicle and OMAV-treated groups. Treatment with 24 mg/kg OMAV started at 3 weeks of age and continued for 5 weeks. Cardiac function was examined in-vivo by echocardiography. We found that FXN cKO mice developed severe heart failure with 45% reduction in ejection fraction, increased left ventricular (LV) mass (+80%) and diameter (+308%), decreased stroke volume (-26%) and cardiac output (-38%, n=10) as compared to WT mice (n=12). Cardiac deficits were more pronounced in FA males compared to females. OMAV (n=14) significantly decreased LV mass (-24%), LV diameter (-28%), and partially recovered a decrease in ejection fraction (+40%), stroke volume (+22%) and cardiac output (+35%). Gene expression of NADP(H) quinoline oxidoreductase-1 (NQO1), superoxide dismutase 2 (SOD2), and glutathione S-transferase were decreased by 60-90% in FA and recovered by 60-90% by OMAV. Aconitase activity, used as a surrogate measure of frataxin's iron-sulfur biogenesis function, was decreased in FA by 49% and recovered 33% by OMAV. Conclusions: This is the first study to demonstrate sexual dimorphism in FA hearts and show that OMAV can improve cardiac function in FA mice with severe cardiomyopathy.
Abstract 13338: Clinical Profile of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction: From the GWTG-HF Registry
Authors: Josephine Harrington, jie-lena sun, Michael Felker, Gary Binder, Robb Kociol, Punag Divanji, Larry A Allen, Brooke Alhanti, Clyde W Yancy, Nancy M Albert, Gregg C Fonarow, Adam D Devore, Stephen J Greene
Journal: Circulation (2022)

Introduction: Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (i.e., stage D HF). The clinical profile, outcomes, and management of these patients in US practice is not well described. Methods: We studied patients hospitalized for worsening chronic HF with reduced ejection fraction (HFrEF) ≤40% across 423 sites in the Get With The Guidelines® (GWTG)-HF registry admitted 2014 -2019. We excluded patients with heart transplantation or durable mechanical circulatory support, severe kidney disease (eGFR&lt;20 mL/min/1.73 m 2 or dialysis), or missing critical data elements. Patients were grouped by EF (≤30% vs. 31-40%) and data were compared using absolute standardized differences. Results: Among 113,348 patients with HFrEF ≤40%, 78,589 (69%) had an EF≤30%. Compared with EF 31-40%, patients with EF≤30% tended to be younger, were less likely to be female, and more likely to be Black (Table). Patients with EF ≤30% had lower systolic blood pressure, but modestly higher eGFR and lower rates of atrial fibrillation and diabetes. Rates of guideline-directed medical therapy (GDMT) use at discharge were generally higher among those with EF≤30%, including greater use of triple therapy (ACEI/ARB/ARNI + beta-blocker + MRA). Among 20,387 patients age ≥65 years linked to Medicare, compared with patients with EF 31-40%, patients with EF≤30% faced higher rates of 12-month mortality and HF hospitalization, but similar rates of all-cause hospitalization. Conclusions: Among patients hospitalized for worsening chronic HFrEF in US clinical practice, most patients have severely reduced EF≤30%. Despite modestly higher use of GDMT at discharge and younger age, patients with severely reduced EF face heightened post-discharge risk of death and HF hospitalization.
Abstract 15305: The Dynamic Behavior of Polymer Microbubbles During Long Ultrasound Tone-Burst Excitation and Its Application for Sonoreperfusion Therapy
Authors: Xucai Chen, Xianghui Chen, jianjun Wang, Francois T.H. Yu, Flordeliza S Villanueva, John Pacella
Journal: Circulation (2022)

Objective: Ultrasound (US)-targeted microbubble (MB) cavitation (UTMC) mediated therapies have been shown to restore perfusion and enhance drug/gene delivery. Due to the potentially longer circulation time and relative ease of storage and reconstitution of polymer shelled MBs compared with lipid MBs, we investigated the dynamic behavior of polymer MBs and its therapeutic potential for sonoreperfusion (SRP) therapy. Methods: We explored the fate of polymer MBs during a single long tone-burst exposure (1 MHz, 5 ms) at various acoustic pressures (0.25-1.5 MPa) and MB concentrations (2х10 6 -2х10 8 MB/mL) via direct high-speed microscopy observation and passive cavitation detection (PCD) and compared with lipid MBs. SRP efficacy of these MBs was investigated in an in vitro constant flow system at various pulse durations (1 MHz, 1-5 ms every 3 sec for 20 min) and acoustic pressures (0.6-1.5 MPa). The pressure differential across a porous mesh partially occluded with microthrombi was recorded as a function of time during treatment and used as a measure of thrombus burden. The terminal pressure drop and the initial rate of pressure drop were derived and compared. Results: Both polymer and lipid MBs first underwent stable or inertial cavitation depending on the acoustic pressure, and then formed gas-filled clusters that continued to oscillate, fragment, and form new gas-filled clusters during the single US burst. PCD confirmed continued acoustic activity throughout the 5-ms US excitation. SRP efficacy with polymer MBs increased with the pulse duration and acoustic pressure ( p &lt;0.05, ANOVA), similarly to that of lipid MBs, but no significant differences were found between polymer and lipid MBs ( Figure 1 ). Conclusion: Under the acoustic conditions tested, both polymer and lipid MBs demonstrate similar thrombolytic effects in vitro suggesting that persistent cavitation activity from polymer MBs during long tone-burst US confers excellent reperfusion efficacy.
Abstract 14399: Novel Mechanisms of Diastolic Dysfunction in Cardiac Aging
Authors: Nastaran Daneshgar, Dao-Fu Dai
Journal: Circulation (2022)

Aging is associated with a progressive decline in cardiac diastolic function. Membranous α-klotho, predominantly produced by the kidney, can be cleaved and form circulating α-klotho, which acts as an anti-aging hormone. Echocardiography showed klotho deficiency in 20-24-month-old heterozygous klotho (KL +/- ) mice aggravates left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) compared with old wild type (OWT) littermates. Supplementation with α-Klotho (0.1mg/kg/day. i.p) for 10 weeks significantly reduced LV mass and ameliorated DD in both OWT and OKL. The improvement in DD was confirmed by Millar catheter measurement of -dP/dt. To gain mechanistic insights, we performed unbiased acetylomics using Acetyl-lysine antibody enrichment, followed by Tandem mass tag proteomics analysis. We identified 1215 lysine acetylation sites (K-Ac) on &gt;1000 cardiac proteins, of which 220 K-Ac sites were significantly hyperacetylated in OWT hearts. There were 63 Ac-K sites &gt;2-fold hyperacetylated in aged hearts (OWT vs. YWT). The comparison of OKL to YWT augmented the number of Ac-K sites to 82. These sites include redox proteins, several metabolic and mitochondrial proteins involved in fatty acid and amino acid metabolism, and the TCA cycle. Several isoforms of myosin heavy chains (MHC) were also hyperacetylated at multiple sites. Some hyperacetylated MHC (e.g. K941) are predicted to alter the molecular structure and relaxation kinetics by Molecular Dynamic Simulation. In addition to delayed Ca 2+ reuptake by myocardial sarcoplasmic reticulum ATPase (SERCA2a), decreased SERCA2a expression and increased acetylated SERCA2 in aged hearts, which was all corrected upon klotho supplementation, we found potential novel mechanisms of DD with hyperacetylation of MHC, concomitant with a decrease in Sirt1 deacetylase, in OWT mice that was aggravated in OKL, which was replenished upon klotho supplementation. Collectively, we demonstrated klotho deficiency aggravates cardiac aging phenotypes, associated with hyperacetylation of several cardiac proteins due to diminished Sirt1. Klotho supplementation rejuvenates several cardiac aging phenotypes, including regression of LVH and improvement of DD, in parallel with reversal of protein acetylation.
Abstract 14411: Transcatheter Closure of Residual Leak Using Gore Cardioform Occluder After Failed Surgical Ligation of Left Atrial Appendage
Authors: Sri Mandava, Akhil Gade, Nethuja Salagundla, Senthil Thambidorai
Journal: Circulation (2022)

Introduction: In non-valvular atrial fibrillation, the left atrial appendage (LAA) is the most common site for thromboembolic formation. The current recommendation is that patients with afib and a CHA2DS2-VASC risk score &gt;2 who undergo cardiac surgery should simultaneously have surgical left atrial appendage closure (Grade 1b). A rare complication that can occur includes incomplete LAA surgical closure with the residual leak, leading to an increased risk of stroke or thromboembolic events. We present two cases with residual leaks on follow-up after surgical ligation of LAA. Methods: Two patients aged 75 to 80 years old with a history of paroxysmal atrial fibrillation, surgical mitral valve repair, and surgical left atrial appendage ligation underwent a transesophageal echocardiogram (TEE) to evaluate the LAA. The CHA2DS2-VASC risk score was 3 for both patients. There was evidence of a residual leak greater than 5 mm between the left atrium and left atrial appendage. Results: Given the residual leak and risk scores, both patients had an increased risk of stroke. Therefore both patients underwent successful transcatheter closure of the left atrial appendage using a 20 mm Gore CARDIOFORM occluder. TEE was used to confirm no residual color flow and confirmed complete closure of the defects. Patients were continued on oral anticoagulation (DOAC) for six weeks with the plan to switch to antiplatelets. Conclusions: Studies have shown that surgical ligation of LAA can result in a residual leak which can increase the risk of systemic embolization. Following failed surgical ligation of LAA, transcatheter closure of residual leak with Gore CARDIOFORM occluder may be a safe and effective strategy for management. Further studies are needed to evaluate the safety, efficacy, and outcomes of utilizing a septal occluder device in patients with residual leaks due to failed surgical ligation of LAA.
Abstract 13496: Sequencing in Over 50,000 Cases Identifies Coding and Structural Variation Underlying Atrial Fibrillation Risk
Authors: Sean J Jurgens, Seung H Choi, Christopher M Haggerty, Ling Xiao, Valerie N Morrill, Nicholas A Marston, Lu C Weng, James P Pirruccello, Matthew C Hill, Christian T Ruff, Marc S Sabatine, Kathryn Lunetta, Steven A Lubitz, Patrick T Ellinor
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. AF is known to have a heritable component, with &gt;100 associated common variant loci. Rare variant studies have yielded limited robust associations for AF. We aimed to utilize large genome and exome sequencing data to discover rare genetic variants conferring large effects on AF risk. Methods: We meta-analyzed genome and exome sequencing data from 36 studies, including TOPMed, CCDG, UK Biobank and FOURIER. We performed exome-wide gene burden testing of rare (MAF&lt;0.1%) loss-of-function and deleterious missense variants, and single variant testing of low-frequency and rare (MAF&lt;1%) coding variants. Within genome sequenced samples, we performed gene burden testing of rare structural variants. Novel signals were replicated in MyCode. Finally, we functionally validated a novel gene by siRNA knockdown in pluripotent-induced atrial cardiomyocytes. Results: We included 52,416 AF cases and 277,762 controls, of which 49.6% were female, 83.4% were of European ancestry, and the mean baseline age was 56 years. In analysis of rare coding variation, we identified 4 novel genes associated with AF, including MYBPC3 (OR 3.5, P =2.1x10 -15 ), LMNA (OR 5.7, P =8.8x10 -11 ), PKP2 (OR 1.9, P =5.2x10 -8 ) and KDM5B (OR 2.3, P =3.0x10 -6 ). These signals were robust to removal of heart failure and cardiomyopathy cases and were replicated in independent datasets. Single variant analysis identified 2 novel signals in FAM189A2 (OR 3.9, P =7.86x10 -8 ) and ZFC3H1 (OR 5.9, P =9.7x10 -8 ). Rare deletions in CTNNA3 (OR 4.5, P =7.0x10 -9 ) were associated with increased AF risk and were supported by independent coding variant analyses, while duplications of GATA4 (OR 0.24, P =2.1x10 -5 ) were associated with reduced AF risk. In functional studies, knockdown of KDM5B resulted in shortening of the atrial action potential duration. Conclusions: Our analyses show the contribution of rare coding and structural variants to AF risk, highlight the shared genetic pathways underlying cardiomyopathy and AF, and implicate the histone demethylase gene KDM5B in AF susceptibility. In sum, we expanded our understanding of the rare variant architecture of this common arrhythmia.
Abstract 14875: Topological Data Analysis of Electronic Health Record Features Predicts Major Cardiovascular Outcomes After Revascularization for Acute Myocardial Infarction
Authors: Javier E Lopez, Esha Datta, Aditya Ballal, Leighton T Izu
Journal: Circulation (2022)

Introduction: Topological data analysis (TDA) is an emerging mathematical technique that imposes structure on a dataset and examines the shapes (or topological features) that arise. The TDA algorithm Mapper Plus is proposed to study the spatial characteristics of clinical data for the purpose of patient classification. This is a data-driven and hypothesis-free approach to clinical risk stratification. Hypothesis: The hypothesis is that Mapper Plus can classify distinctive subsets of patients receiving optimal treatments post-acute myocardial infarction (AMI). Our goal is to identify subgroups who remained at risk of having a future adverse event (AE) i.e., death, heart failure hospitalization, or recurrent MI Methods: A single-center, retrospective analysis of 31 clinical variables from the electronic health record (EHR) was conducted on 798 AMI subjects. Risk was defined as high or low in relation to the average probability of survival without AE for the entire cohort at the 1 year mark. Results: TDA identified six subsets of patients. Four subsets (n=597) had &gt; 1-fold change on the probability of survival free of AEs; these became the low-risk subgroup. Two subsets (n=344) had &lt; 1-fold change on the probability of survival free of AEs; these became the high-risk subgroup. Because Mapper Plus allows for subject overlap across subgroups, 143 subject (18%) were shared between the high (n=201, 25%)- and low-risk (n=454, 57%) subgroups and were extracted into a 3rd intermediate risk subgroup (see figure). Conclusions: TDA significantly stratified AMI patients into 3 subgroups with distinctive incidences of AE up to 3 years post AMI. This is a new framework for EHR-based risk stratification that requires no additional patient interaction, is agnostic to prior knowledge, and is driven by the topological features of the included data. Further studies will be needed to validate TDA across different patient cohorts before it can be applied to clinical practice.